This proposal is to request support for a Keystone Symposia meeting entitled "Structural Biology", organized by Pamela J. Bjorkman and Andrej Sali, which will be held in Breckenridge, Colorado from January 8 - 13, 2010. Static depictions are appearing in ever-increasing numbers of the detailed structures of individual macromolecules. A key challenge for structural biology is how to parlay this reservoir of fundamental information into a comparably detailed understanding of how functional complexes assemble;what ranges of alternative conformations they may assume at successive stages of their functional cycles;how they recognize each other;and how their propensities to bind small molecules, cofactors and other macromolecules are specified;and how they behave in cells. This meeting will explore ongoing developments in structural biology on several fronts including the following: the frontier between in vitro and in situ observations;the frontier between traditional experimental approaches and newly emerging complementary ones;and the frontier represented by computational structural biology as a means to analyze, integrate, and unify information emerging from diverse experimental sources. Opportunities for interdisciplinary interactions will be further enhanced by the concurrent meeting "Structural Genomics: Expanding the Horizons of Structural Biology", which will share the opening keynote session and two plenary sessions with this meeting. PUBLIC HEALTH RELEVANCE: There has been an explosive growth in the amount of structural information available on macromolecular systems such as proteins, nucleic acids, and their complexes. These insights and those derived from complementary studies are proving important for understanding the molecular basis for diseases and for the development of new therapeutic approaches to treating human disorders. The Keystone Symposia meeting on Structural Biology will focus on recent developments in structural biology and their impact on the understanding of key biological problems.